1. 1-0199 Botulinum in the Research Laboratory - EHS Controls Presented by: Lisa Wisser, CIH AIHCE - June 6, 2001

2. 1-0199 Outline Botulinum Background Botulinum Background Exposure Controls Exposure Controls –Engineering –Administrative –PPE Program Management Program Management

3. 1-0199 What is Botulinum Toxin? Produced by Clostridium botulinum Produced by Clostridium botulinum Toxic effect on axons of motor neurons Toxic effect on axons of motor neurons –Prevents release of acetylcholine, blocking neuromuscular transmission –Causes cranial nerve and skeletal muscle paralysis

4. 1-0199 More on Botulinum Toxin LD 50 (mouse) = 1 ng/kg LD 50 (mouse) = 1 ng/kg

5. 1-0199 Exposure Controls Laboratory design requirements Laboratory design requirements –Codes: UBC, UFC –OSHA regulations: 8 CCR 5191 (CHP) and 8 CCR 5154 (fume hoods/biosafety cabinets) –CDC/NIH Biosafety in Microbiological and Biomedical Laboratories (BMBL), Guidelines for Work with Toxins of Biological Origin

6. 1-0199 Laboratory design issues for this project Laboratory design issues for this project –Ventilation –Access control –Storage Engineering Controls

7. 1-0199 Ventilation Establish pressure differentials Establish pressure differentials Local exhaust ventilation Local exhaust ventilation –Bench-top fume hood –Biosafety cabinet –Problem - not enough LEV for both (+) (-) (--) FH BSC

8. 1-0199 Ventilation Biosafety Cabinet vs. Fume Hood Biosafety Cabinet vs. Fume Hood

9. 1-0199 Access Control and Storage Why? Bot toxin is a Select Agent Why? Bot toxin is a Select Agent What: What: –Key lock for main door –Padlocks for refrigerator, freezer, incubator (+) (-) (--) FH BSC I R F

10. 1-0199 Administrative Controls Laboratory Registration/Select Agent Transfer Program Laboratory Registration/Select Agent Transfer Program –42 CFR 72.6: Additional requirements for facilities transferring or receiving select agents n From the Antiterrorism and Effective Death Penalty Act of 1996 –Requires registration with the CDC

11. 1-0199 Administrative Controls Approval by Institutional Biosafety Committee Approval by Institutional Biosafety Committee –Biological Use Authorization form Chemical Hygiene Plan Chemical Hygiene Plan –Toxin-specific addendum n checklist for facility requirements n work practices n emergency procedures (spills and exposures) n toxin information

12. 1-0199 Administrative Controls Training Training –Laboratory biosafety –Toxin-specific session –Annual refresher with Occupational Physician Medical Surveillance Medical Surveillance –Vaccine and antitoxin available

13. 1-0199 Administrative Controls Inventory Control System Inventory Control System –Locked storage areas –Inventory control log n amount received n amount removed, by whom, date n amount remaining n final disposition

14. 1-0199 Administrative Controls Sign, Labels, etc. Sign, Labels, etc. – Toxins in Use - Authorized Personnel Only on door –Biohazard labels –MSDSs in lab

15. 1-0199 Administrative Controls Decontamination Decontamination Waste handling Waste handling BLEACH

16. 1-0199 PPE

17. Program Management Management by Inspection Management by Inspection –Locks and inventory log –Work practices –PPE –Waste Continuous review and improvement Continuous review and improvement –e.g., emergency procedures, waste handling

18. 1-0199 Summary Botulinum toxin = potential hazard Botulinum toxin = potential hazard Ensure facility is adequate to control hazard Ensure facility is adequate to control hazard Impose myriad of administrative controls; provide assistance in meeting requirements Impose myriad of administrative controls; provide assistance in meeting requirements Update the program as needed Update the program as needed

19. 1-0199 Useful Resources http://www.cdc.gov/od/ohs/default.htm (CDC OHS) http://www.cdc.gov/od/ohs/default.htm (CDC OHS) http://www.cdc.gov/od/ohs/biosfty/bmbl4/b mbl4toc.htm (BMBL) http://www.cdc.gov/od/ohs/biosfty/bmbl4/b mbl4toc.htm (BMBL) http://www.cdc.gov/od/ohs/lrsat.htm (LR/SAT) http://www.cdc.gov/od/ohs/lrsat.htm (LR/SAT) http://www.absa.org/ http://www.absa.org/ http://www.dir.ca.gov (Cal-OSHA regulations) http://www.dir.ca.gov (Cal-OSHA regulations)